Particle beam radiation therapy (PBRT) has identified strengths compared conventional electron or photon radiation therapy, particularly the favorable depth dose distributions. However, there are still numerous open questions and concerns that should be addressed before it is fully implemented in cancer care. Substantial pre-clinical, clinical, physics, socio-economic and cost benefit research is needed. The application herein lays out the necessary groundwork for the establishment of the National Particle Therapy Research Center (NPTRC). It will be affiliated with the final phase, i.e., the 12C therapy facility of the Texas Center for Advanced Radiation Therapy (TCART), a new tri-modality treatment center at University of Southwestern Medical Center including a conventional photon radiation therapy facility (funded) with 13 linear accelerator bunkers, a connected proton therapy facility (under construction) housing a Varian Cyclotron with 4 full gantries and one fixed-beam room, and ultimately a heavy ion facility (being planned). With the creation of the NPTRC, researchers from across the nation can use the resources to conduct research organized at the national level: in particle and medical physics aimed at the clinical use of charged particles; in radiobiology to better understand the underlying biological mechanisms of tumor and normal tissue response; and in testing the efficacy of PBRT through human clinical trials. The vision of the NPTRC, and particularly how it integrates with the PBRT facility, requires consideration into the optimal structure, layout, infrastructure, and physical and operating configurations. The main goal of this Planning Grant is to design and plan this national research center (NPTRC) through (1) the identification of the research directions, (2) the development of the research beam line specifications, (3) the recruitment of the relevant expertise needed, (4) the development of research collaborations and consortia, and (5) the development of common platforms for collaborative research. This goal will be achieved by pursuing three specific aims. (1) To develop the specifications of the research beam- line and related infrastructure for the NPTRC research activities (Pilot Project #1). (2) To develop a Monte Carlo simulation platform using novel graphics-processing unit (GPU) and cloud computing technologies for PBRT (Pilot Project #2). (3) To establish the overall research directions and develop the necessary infrastructure to support and manage future research activities (Administrative Core and Pilot Project #1). The successful completion of these specific aims will position the NPTRC to coordinate large-scale research projects related to PBRT, develop outreach and training in the use of PBRT and ultimately provide cutting edge patient care and support through TCART.